Sirna Therapeutics, Inc.

Transcription

1 Sirna Therapeutics, Inc. Brean Murray, Carret & Co. Small Cap Institutional Investor Conference February 2006

2 Forward Looking Statements Statements in this presentation which are not strictly historical are "forward-looking" statements which should be considered as subject to many risks and uncertainties. For example, Sirna's ability to operate as a going concern is contingent upon having readily available cash to fund its operating programs including the escalating expenses and risks associated with the initiation of clinical trials and their potential outcomes. Other risks and uncertainties include Sirna's early stage of development and short operating history, whether Sirna can achieve and maintain profitability, whether Sirna can obtain and protect patents, the risk of third-party patent infringement claims, whether Sirna can engage collaborators and obtain regulatory approval for products, Sirna's concentration of stock ownership, and availability of materials for product manufacturing. These and additional risk factors are identified in Sirna's Securities and Exchange Commission filings, including the Forms 10-K and 10-Q and in other SEC filings. Sirna undertakes no obligation to revise or update any forward-looking statements in order to reflect events or circumstances that may arise after the date of this release.

3 RNA Interference The most exciting discovery in biology in the last decade Areas to Watch in 2006 RNAi-based treatments. They re moving into human patients with startling speed, and 2006 should offer the first hints of how well the highly touted technique works. Company-funded trials in macular degeneration and the pediatric illness respiratory syncytial virus are under way; another targeting hepatitis C is supposed to launch soon, with some therapies for neurological diseases to follow. Oh, and another treatment that s coming down the pike: RNAi for permanent hair removal.

4 RNAi - based Therapeutics The next important drug class to impact human health > Potent and specific therapeutic effect utilizing an endogenous cellular mechanism > Selectively silences expression of pathological proteins and viral targets > Powerful catalytic mechanism > Applicable to classically non-druggable targets

5 Making RNAi-based Therapeutics a Reality Impact of Sirna s Chemistry Expertise The critical requirements to develop sirna therapeutics modification and formulation Serum Stability Half Life Circulation Time Tissue Targeting Duration of RNAi Activity Immune Response Unmodified sirnas < 1 min < 15 mins < 0.1% < 2 days Stimulatory Sirna s Compounds 17 days 4 days 70% 22 days Regulated

6 Research and Development Programs Leveraging Chemistry and Delivery Across Multiple Therapeutic Areas Huntington s Disease Sirna target: HUNTINGTON Gene Oncology AMD Sirna target: VEGFR-1 Respiratory Sirna target: IL-4, IL-4R, IL-13, IL-13R Viral Hepatitis Sirna target: HBV/HCV Diabetes Sirna target: Phosphatase 1B (PTP1B) Dermatology Sirna target: HAIRLESS TXN Factor

7 Age-Related Macular Degeneration Major cause of blindness in the US > 500,000 new cases per year worldwide (40% US) > Estimated $1.7 billion market opportunity by 2007 (1) > High unmet medical need > Huge opportunity for novel therapeutics > Efficacy > Safety > Dosing Regimen (1) CSFB Equity Research

8 Single Dose Visual Acuity Comparison 100% Sirna weeks 100% Lucentis 4 weeks 89% Patient Incidence 23% 26% 0% 0% 0% Sirna-027 (N=22) 11% 11% Lucentis (N=27) Any Deterioration Significant Improvement ( 3 Lines) Significant Deterioration ( 3 Lines) Stable/Improved

9 Demonstrated Safety and Tolerability No ocular inflammation observed with Sirna % 33% Patient Incidence 11% 0% 0% 0% Sirna-027 (N=22) Lucentis (N=27) Clinically Significant Inflammation Mild Inflammation

10 Strategic Alliance with Allergan in Ocular Diseases > Strategic alliance in ocular disease with a global leader in eye care > $5MM initial payment > Up to $245MM clinical milestones > Worldwide royalties > Allergan is responsible for development of Sirna-027 > Phase II initiation planned for Q > Collaboration leverages the strengths of both companies to develop novel and innovative ocular therapeutics > Sirna develops optimized sirna lead compounds > Allergan conducts and funds all pre-clinical development, clinical, regulatory, and commercialization activities > Allergan provides proprietary and novel delivery technologies

11 Pioneering Systemic sirna Delivery Viral Hepatitis Programs > Hepatitis C > 2.7 million US afflicted > $1 billion market worldwide > Hepatitis B > US ~ 1.25 million are chronic carriers > ~ 400 million chronic cases worldwide > Chronic HBV/HCV leads to fibrosis, cirrhosis, hepatocellular carcinoma and acute liver failure

12 Pioneering Systemic sirna Delivery Key Achievements in Viral Hepatitis > Chemically optimized sirnas which can target the conserved region of viral genome > sirna-based compounds designed to target multiple viral sequences to reduce drug resistant mutations > Sirna nanoparticle formulation targeting hepatocytes > Standard I.V. administration at low doses > Systemic efficacy in murine and non-human primate models

13 99.9% Reduction of HBV in Murine Model Day 3 Day 7 Serum HBsAg % Reduction Active sirna Control PBS Active sirna Control PBS 0.1 3mg/kg/day x 3 days

14 Anti-HBV sirna Dose Response in Murine Model 1000 Serum HBsAg PBS Active Control mg/kg/day x 3 days

15 HCV Primate Study > Three animals were infected with an HCV chimeric virus > Administered Sirna nanoparticle formulated, multisirna compound > Objective > Demonstrate delay in onset of establishment of viral infection > Demonstrate knock-down of viral load after established infection > Endpoints - safety and efficacy

16 sirna Mediated Knockdown of HCV Chimeric Infection in Non-Human Primate Model Log Serum Titers untreated Three non-human primates were infected with an HCV chimeric virus at time zero 99.5% inhibition 3 wk delay in onset of 3.5 LOQ established infection Weeks 1-8 Dose = 3mg/kg

17 Summary of sirna mediated inhibition of HCV in Non-Human Primates > Efficacy > Delayed onset of establishment of viral infection > Demonstrated a 99.5% reduction in viral titers in an established infection > Safety > No increase in liver enzymes observed > Mechanism of Action > sirna-mediated target cleavage products detected by RACE analysis

18 Sirna-AV34 Development Candidate for Treatment of HCV > Sirna-AV34 targets multiple HCV sequences and is designed to reduce drug resistant mutations > Pre-IND with FDA planned for February 2006 > IND to be filed by Q4 2006

19 Asthma >Asthma is a chronic respiratory disease affecting 15 million children and adults in the U.S. > $13 billion in annual health care costs >Airway Hyperresponsiveness (AHR) is the hallmark of asthma in humans >AHR results from damage to the airway wall caused by TH-2 cytokine-dependent airway inflammation

20 Lipid Nanoparticle Formulation of sirna Prolongs Lung Exposure after Aerosol Lung Delivery (20µg Single Dose) Unformulated Nanoparticle Duplex (μg/ml) Days 1-8

21 Nanoparticle formulated sirna Targeting IL-4Rα Inhibits Lung Inflammation Percentage of Asthma Marker in Lungs (eosinophils) 80% 70% 60% 50% 40% 30% 20% 10% 0% 70% Reduction Naïve 1.0 mgkg 0.01 mg/kg Vehicle Target = IL-4Rα IL-4a

22 Nanoparticle sirna Targeting IL-4Rα Inhibits Airway Hyperresponsiveness 1.0 mg/kg Nanoparticle sirna 0.1 mg/kg Nanoparticle sirna 0.01 mg/kg Nanoparticle sirna Vehicle Naive 80% Inhibition of AHR

23 Dominant Patent Estate in RNAi-based Therapeutics > Sirna s patent estate covers every aspect of drug design, synthesis, development & manufacturing > Use > Targets > Technology > Chemistry > Delivery > Manufacturing 49 Issued and over 240 Pending Patents Worldwide

24 Multi-Sequence Gene Targets Therapeutic Area Targets Metabolic PTP1B JNK1 p38 GIP SCD ERK-1 CETP ACADB Myostatin Oncology Her-2 RAF RelA Ras EGFR K-ras CHK1 c-fos PKC-α ERG-2 c-myc MDR-1 Egr-1 VEGFR p38 VEGF GAB2 Bcl2 c-jun PCNA XIAP cdk2 JNK1 Telomerase ECGF1 PRL3 ERG IGF-1R c-myb ERK-1 EGF-1 EZH2 HIF1 BCR/ABL Cyclin-D1 ANG-1 B7-H1 PDGF PDGF (R) P1GF-1 htr VCAM Inflammation/Fibrosis/ IGF-1R REL-A GAB2 p38 TGF-β TGF- βr c-fos Respiratory VEGF VEGFR IL4-R ADAM33 ANG-1 CHRM3 CXCR5 FAS GPRA ICAM IKK-g IL-2 IL-4 IL-8 IL-13 IL-13R VCAM MMP13 IL-9 IL-5 RSV Cardiovascular/Renal c-myc c-myb VEGF VEGFR PCNA Egr-1 ANG-1 PDGF (R) FAS Neurology BACE (β-secretase) APP HD presenilins NOGO NOGOR Alpha-synuclein PARK2 SCA1 TRPM7 Infectious Diseases HCV HIV CCR-5 HBV SARS c-jun RSV Ocular VEGF VEGFR IGF-1R TGF- β TGF-b R ANG-1 PlGF-1 Dermatology IKK-g Connexin43 Hairless B7-H1 VDR WHN EGFR WNT3A STAT3 Desmoglein-4 5-a-reductase IL-2 TNF a IL-4 IL-13

25 Sirna s RNAi IP Leadership Technology IP No Ribo sinas sina for Greater Potency and Stability Multifunctional sirnas Target Multiple Genes Simultaneously Micro RNAs Chemically-modified mirnas Conserved Sequence Targeting Multiple Genes or viral strains Licensed IP Tuschl, et.al. sirna for Therapeutic Use B. Davidson U of Iowa Huntington s & Other Neurological Indications A. Christiano Columbia Hair Removal Hair Growth Rana, et.al. UMASS Chemical Optimization Target IP AMD HD Hairless Asthma Hepatitis Diabetes VEGF Pathway HD Gene Hairless TX Factor IL-4 IL-4R IL-13 IL-13R HBV HCV PTP-1B Chemistry & Delivery IP Chemistry Chemically Modified sirna Improved PK Stability Potency Inhibition of Immune-stimulation Delivery Tissue & Cell Targeting Nanoparticles Conjugates Manufacturing IP Manufacturing Process Development Scale-Up cgmp manufacturing Raw Materials Reagents

26 Sirna Collaboration and Proprietary Pipeline Collaboration Programs Allergan - Sirna-027 (AMD) Allergan Ocular Targets Targeted Genetics - Huntington s Discovery Pre-Clinical Clinical IND-PH1 PH2 Q Proprietary Programs Hepatitis C Hepatitis B Hairless Asthma Interleukin 4 Asthma Interleukin 13 Respiratory/Inflammation - P38 MAPK Diabetes Phosphatase-1B Hearing Loss Retinoblastoma 1 Q Q4 2006

27 Financial Highlights > Revenues Q $1.9M > Cash balance as of $44.7M > Allergan Q4 Cash $5.0M > Forecast 2005 year-end cash balance $43-$45M

28 Key Value Drivers > Collaboration Programs > Initiate Phase II on Sirna-027 in 2Q 2006 > Establish at least one major corporate partnership > Proprietary Programs > HCV Program File IND in 4Q 2006 > Hair Removal Program File IND in 4Q 2006 > Asthma Identify Clinical Development Candidate > Intellectual Property > Issuance of key sirna patents in the United States

29 Forward Looking Statements Statements in this presentation which are not strictly historical are "forward-looking" statements which should be considered as subject to many risks and uncertainties. For example, Sirna's ability to operate as a going concern is contingent upon having readily available cash to fund its operating programs including the escalating expenses and risks associated with the initiation of clinical trials and their potential outcomes. Other risks and uncertainties include Sirna's early stage of development and short operating history, whether Sirna can achieve and maintain profitability, whether Sirna can obtain and protect patents, the risk of third-party patent infringement claims, whether Sirna can engage collaborators and obtain regulatory approval for products, Sirna's concentration of stock ownership, and availability of materials for product manufacturing. These and additional risk factors are identified in Sirna's Securities and Exchange Commission filings, including the Forms 10-K and 10-Q and in other SEC filings. Sirna undertakes no obligation to revise or update any forward-looking statements in order to reflect events or circumstances that may arise after the date of this release.

30 Sirna Therapeutics, Inc. Brean Murray, Carret & Co. Small Cap Institutional Investor Conference February 2006